With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

Objectives This study evaluated the utility of Patient-Reported Outcomes Measure Information System Depression Scale (PROMIS-8a) compared to selected “Legacy” depression scales including Montgomery-Asberg Depression Rating Scale (MADRS), Geriatric Depression Scale (GDS), and GDS-Short Form (GDS-SF). Additionally, the measures’ properties were assessed across levels of cognitive functioning. Methods This cross-sectional analysis was extracted from a prospective cohort study. PROMIS-8a and Legacy depression measures were administered to individuals aged ≥70 grouped by cognitive status based on the Saint Louis University Mental Status Examination. McNemar tests were run to determine if measures categorized the absence or presence of depression differently and item analysis evaluated classification discrepancies. Results Sample mean age was 78, the majority was female (71%), Caucasian (79%), with at least a high-school education (89%). The percentage of individuals with at least mild depression was similar across measures (20.7% PROMIS-8a; 19.0% MADRS; 17.9% GDS; 13.9% GDS-SF). PROMIS-8a total score correlated moderately with MADRS (r=.56, df=295, p<.01), GDS (r=.68, df=291, p<.01), and GDS-SF (r=.60, df=291, p<.01) and predictive validity of the measures was similar. There were no significant mean differences on depression measures by cognitive status. Conclusions While all measures identified a similar percent of depressed individuals, the classification differed by measure. Item analysis showed that PROMIS-8a was more likely to identify feelings of dysphoria, and the MADRS and GDS were more likely to identify physiological aspects of depression. Given the brevity and ease of administration of the PROMIS-8a, it appears to be a useful depression screen for community-dwelling older adults.